全文获取类型
收费全文 | 2901篇 |
免费 | 189篇 |
国内免费 | 2篇 |
专业分类
3092篇 |
出版年
2023年 | 7篇 |
2022年 | 17篇 |
2021年 | 35篇 |
2020年 | 33篇 |
2019年 | 35篇 |
2018年 | 44篇 |
2017年 | 39篇 |
2016年 | 62篇 |
2015年 | 92篇 |
2014年 | 131篇 |
2013年 | 167篇 |
2012年 | 204篇 |
2011年 | 190篇 |
2010年 | 145篇 |
2009年 | 135篇 |
2008年 | 176篇 |
2007年 | 193篇 |
2006年 | 190篇 |
2005年 | 176篇 |
2004年 | 156篇 |
2003年 | 149篇 |
2002年 | 138篇 |
2001年 | 27篇 |
2000年 | 29篇 |
1999年 | 42篇 |
1998年 | 47篇 |
1997年 | 33篇 |
1996年 | 27篇 |
1995年 | 24篇 |
1994年 | 32篇 |
1993年 | 23篇 |
1992年 | 27篇 |
1991年 | 26篇 |
1990年 | 23篇 |
1989年 | 17篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 21篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1977年 | 6篇 |
1976年 | 10篇 |
1975年 | 6篇 |
1974年 | 10篇 |
1973年 | 7篇 |
排序方式: 共有3092条查询结果,搜索用时 15 毫秒
21.
Bernard Longpré Prométéo Madarnas Léo Cousineau Marcel Rochon Serge Filion 《CMAJ》1974,110(6):645-648
Scleronodular type of Hodgkin''s disease: experience at the Centre hospitalier universitaire de SherbrookeThe nodular sclerosis type of Hodgkin''s disease appears to be a distinct clinical entity. However, the incidence, the initial localization of the tumour and the survival of the patients are variable. The present study was carried out on a group of 17 patients, all French Canadians living in the province of Quebec, from a total of 31 with Hodgkin''s disease, an incidence of 55%. There were more males (10) than females (7). The mean age of the group was 37 years, but that of the females was lower than that of the males. The mediastinum was involved at the onset in 47% of the patients. The initial staging (according to the classification of Rye) in 76% of the patients was I or II.Four patients showed disease below the diaphragm. The lungs were infiltrated three times, the spleen six times, and the liver five times. The duration of survival of the 17 patients was twice that of the patients with the three other types of the disease. 相似文献
22.
Summary Oxidative and hydrolytic enzyme activities are present in the anlage of the human basal ganglia as early as the second month of embryonic life, and acetylcholinesterase activity appears during the sixth month of pre-natal life.Clinical Research Fellow of the Medical Research Council. Presently in the Department of Neurology, Indiana University, Medical School. 相似文献
23.
24.
Philip W. Beesley Toni Paladino Irene Hill Claude Gravel Richard B. Hawkes James W. Gurd 《Journal of neurochemistry》1990,54(2):505-512
Glycoprotein gp50 is a neurone-specific, granule cell-enriched glycoprotein that is also a major component of isolated synaptic membranes. Here, we describe the use of a monoclonal antibody, mab SM gp50, to study the postnatal development of gp50 in the brain of normal and thyroid-deficient rats. Radioimmunoassay, enzyme-linked immunosorbent assay, and Western blotting show that gp50 is not detectable in brain until postnatal day 4 (P4) in both forebrain and cerebellum. In forebrain, the rate of increase of gp50 levels is maximal between P12 and P20. It is somewhat later in cerebellum, where peak levels are attained between P30 and P35. Immunocytochemical studies show little detectable gp50-like immunoreactivity before P16, and the staining is still weak, relative to adult tissue, at P25. The intense staining of the granule cell layer characteristic of adult cerebellum predominantly appears after P25. Development of gp50 is severely retarded in the cerebellum of thyroid-deficient rats, particularly during the second and third postnatal weeks. However, by the fourth postnatal week, gp50 levels in normal and hypothyroid animals are comparable. The results indicate that significant alterations in the pattern of gp50 expression continue to occur at a late stage of cerebellar development. In particular, the increase in immunocytochemical staining of the granule cells after P25 is striking in that by this time most major events associated with cerebellar development are essentially complete. 相似文献
25.
C A Brown K Neote A Leung R A Gravel D J Mahuran 《The Journal of biological chemistry》1989,264(36):21705-21710
Lysosomal beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52) occurs in two major isozyme forms, hexosaminidase A (alpha beta) and hexosaminidase B (beta beta). Although dimer formation is required for enzymatic activity, both subunits contain active sites which share many common substrates. However, the alpha subunit alone confers on hexosaminidase A the specificity for negatively charged substrates, e.g. GM2 ganglioside. Recently, a point mutation, producing a single amino acid substitution in the alpha subunit (Arg178-His), has been found to be associated with the B1 variant phenotype of Tay-Sachs disease (Ohno, K., and Suzuki, K. (1988) J. Neurochem. 50, 316-318). This variant is characterized by normal levels of hexosaminidase A as measured by a common artificial substrate, but an absence of activity toward alpha subunit-specific substrates. However, because of the presence of an active beta subunit in the mutant hexosaminidase A, it has not been possible to determine whether the affected alpha subunit has undergone a change in substrate specificity or become totally inactive. In order to define the full effect of the B1 mutation we have taken advantage of the common evolutionary origin of the genes coding for the alpha and beta subunits. Since the B1 mutation occurs in a region of extended identity between the two subunits, we have duplicated the Arg178-His mutation in a cDNA coding for the human beta subunit (Arg211-His). By expression of the mutant construct in monkey COS cells we have been able to examine the effect of this mutation on beta subunits which are capable of forming stable, active homodimers, an experiment that could not readily be accomplished with heterodimeric hexosaminidase A. Our data show that beta homodimers containing the Arg211-His substitution are formed and are transported into the lysosome in a manner identical to that of normal pro-hexosaminidase B. However, the mutant homodimers are processed at a slower rate and are less stable in the lysozyme. Their most striking feature was a total lack of normal hexosaminidase B activity. We conclude that while the effect of the Arg178-His substitution is not strictly limited to the active site, the severe B1 phenotype results from a totally inactive alpha-subunit in hexosaminidase A. 相似文献
26.
Effects of the Phosphatase Inhibitors Calyculin A and Okadaic Acid on Acetylcholine Synthesis and Content of Rat Hippocampal Formation 总被引:2,自引:2,他引:0
Abstract: The biochemical mechanisms involved in the regulation of acetylcholine (ACh) turnover are poorly understood. In the experiments reported here, we examined whether inhibition of the serine/threonine phosphatases 1 and 2A by calyculin A or okadaic acid alters ACh synthesis by rat hippocampal preparations. With hippocampal slices, calyculin A (50 n M ) and okadaic acid (50 n M ) reduced significantly ( p < 0.01) the synthesis of [3 H]ACh from [3 H]choline. Both calyculin A and okadaic acid produced significant depletion of endogenous tissue ACh in a concentration-dependent manner ( p < 0.01). This depletion was not the result of a drug-induced increase of spontaneous ACh release, which was not changed significantly ( p > 0.7) by either drug. Choline acetyltransferase (ChAT) activity from tissue exposed to calyculin A or okadaic acid was reduced in a concentration-dependent manner ( p < 0.05), but these phosphatase inhibitors did not act directly on ChAT in vitro; i.e., enzymatic activity was not altered significantly ( p > 0.4) in the presence of calyculin A or okadaic acid. Both high-affinity and low-affinity [3 H]choline uptake by hippocampal synaptosomes were reduced significantly in a concentration-dependent manner in the presence of calyculin A or okadaic acid; these agents reduced V max values for high- and low-affinity choline uptake ( p < 0.01) with no significant change in K m values ( p > 0.1), indicating a noncompetitive inhibition. Taken together, these data suggest that phosphatase activity plays a role in presynaptic central cholinergic nerve terminal function, in particular in the modulation of ACh synthesis. 相似文献
27.
Frenette Jean-Jacques; Demers Serge; Legendre Louis; Boule Michel 《Journal of plankton research》1996,18(1):45-61
Phytoplankton photosynthetic responses were studied in two basinsof an oligotrophic lake (Québec, Canada). which are characterizedby the absence (shallow Basin 1) and presence (deeper Basin2) of seasonal thermal stratification. Size-fractionated photosynthesiswas used to characterize changes in phytoplankton characteristicsduring periods of seasonal mixing and stratification. Seasonalvariations of P max showed size-related differences, with maximumvalues in July for the picoplankton and in November for thenanoplankton. Similar patterns of variability in 相似文献
28.
Josiane Girardie Adrien Girardie Alain Van Dorsselaer Odile Sorokine Serge Geoffre Michel Hospital Gilles Precigoux 《Journal of peptide science》1995,1(5):311-318
An original insect neurohormone of 65 residues was synthesized by the solid-phase methodology using t-Boc strategy and Boc-Val-PAM–resin. The purification, conducted by several steps of liquid chromatography having mass, polarity or charge as separative criteria, yielded the product with the correct molecular weight of 6922 Da determined by mass spectrometry. The synthetic peptide had both the same affinity for the antinative neurohormone serum and the same biological activity as the native neurohormone. 相似文献
29.
Anne Imberty Florence Casset Colin V. Gegg Marilynn E. Etzler Serge Pérez 《Glycoconjugate journal》1994,11(5):400-413
The three-dimensional structure ofDolichos biflorus seed lectin has been constructed using five legume lectins for which high resolution crystal structures were available. The validity of the resulting model has been thoroughly investigated. Final structure optimization was conducted for the lectin complexed with GalNAc, providing thereby the first three-dimensional structure of lectin/GalNAc complex. The role of theN-acetyl group was clearly evidenced by the occurrence of a strong hydrogen bond between the protein and the carbonyl oxygen of the carbohydrate and by hydrophobic interaction between the methyl group and aromatic amino acids. Since the lectin specificity is maximum for the Forssman disaccharide GalNAc(1–3)GalNAc-O-Me and the blood group A trisaccharide GalNAc(1–3)[Fuc(1–2)]Gal-O-Me, the complexes with these oligosaccharides have been also modelled. 相似文献
30.
R. A. Gravel B. R. Akerman A. M. Lamhonwah M. Loyer A. Lon-del-Rio I. Italiano 《American journal of human genetics》1994,55(1):51-58
Deficiency of propionyl-CoA carboxylase (PCC; alpha 4 beta 4) results in the rare, autosomal recessive disease propionic acidemia. Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA (alpha-subunit) and PCCB (beta-subunit) genes, respectively. The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect interallelic complementation between certain mutations of the PCCB gene. In this study, we have identified the mutations in two pccB, one pccC, and two pccBC cell lines and have deduced those alleles participating in interallelic complementation. One pccB line was a compound heterozygote of Pro228Leu and Asn536Asp. The latter mutation was also detected in a noncomplementing pccBC line. This leaves Pro228Leu responsible for complementation in the pccB cells. The second pccB line contained an insertional duplication, dupKICK140-143, and a splice mutation IVS + 1 G-->T, located after Lys466. We suggest that the dupKICK mutation is the complementing allele, since the second allele is incompatible with normal splicing. The pccC line studied was homozygous for Arg410Trp, which is necessarily the complementing allele in that line. For a second pccC line, we previously had proposed that delta Ile408 was the complementing allele. We now show that its second allele, "Ins.Del," a 14-bp deletion replaced by a 12-bp insertion beginning at codon 407, fails to complement in homozygous form. We conclude that the interallelic complementation results from mutations in domains that can interact between beta-subunits in the PCC heteromer to restore enzymatic function. On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, we suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site. 相似文献